Following previous studies where we developed some high performance porphyrin derivatives for
photodynamic therapy demonstrating their activity in different cell lines, we now extend our attention to CRL1472
bladder cancer line. In this work the phototoxicity of several diaryl and tetraarylporphyrins with different structures were
evaluated with different incubation times. The phototoxicity observed was not directly related to the concentration of
photosensitizer inside cells. Uptake studies demonstrate that the brominated derivative 2 which despite the most efficient
photosensitizer presents a poor tendency to enter into cells.
Starting from expertise in the area of chemical synthesis, particularly in tetrapyrrolic macrocycles and an
interest in modelling structures for particular objectives, we came to the point of aiming at modelling photochemical
sensitizers designed for photodynamic therapy (PDT) purposes. Our endeavours were gratifying when it was proved that
our synthetic methodologies allowed for the easy availability of properly halogenated porphyrins with high quantum
yield singlet oxygen efficiency. Joining the presence of this heavy atom and other functionalities as substituents in
selected positions of macrocyclic structures we were able to generate novel porphyrin structures whose photophysical
and photochemical properties, singlet oxygen formation quantum yields, photobleaching and logP were measured.
Cellular uptake measurements and cytotoxicity assays on WiDr adenocarcinoma and A375 tumor cell lines were carried
out and some of our porphyrins demonstrated very high performance as PDT sensitizers comparatively to known
compounds approved for clinical use and in the market. Further developments of our studies allowed for the generation
of different and more efficient structures, easily made available by our own synthetic methodologies.
Our studies in this area allowed us to reach a stage which we believe to correspond to a significant knowledge
and capacity to synthesise a broad range of simple structures, whose selectivity and efficiency as PDT sensitizers can be
modulated for different cellular and tissue specificities.
Our most recent developments in this area will be presented in this communication.